Reconstituting detergent solubilized integral membrane proteins into unilamellar lipid vesicles offers the possiblitiy of studying the function of these molecules in an environment which resembles their native state. In addition, the ability to efficiently fust protein-containing vesicles with the plasma membrane of cultured cells might allow the dissection and reconstitution of complex membrane-mediated processes in a living cell. This methodology would also permit studies on the effect of chemical or enzymatic modifications on the function and metabolism of specific cell surface proteins. The proposed experiments are designed to test the feasibility of using unilamellar lipid vesicles as vehicles for the insertaion of functional exogenous protein molecules into the plasma membrane of cultured fibroblasts. Initial studies will be directed towards defining conditions which will allow efficient attachment of vesicles to the cell surface. Fusion between the bound liposomes and the plasma membrane will be attempted with polyethylene glycol, n-hexyl bromide, or fusogenic proteins from paramyxoviruses. The model system employed will be the rescue of conditional mutants in the envelope protein of vesicular stomatitis virus by vesicles bearing native, wild type envelope protein. If rescue is obtained, further studies on the incorporation of modified envelope proteins into maturing vesicular stomatitis virus particles will be initiated. These experiments should add to our understanding of how specific viral or cell surface proteins are selected for inclusion into the budding virion envelope. Finally, the ability to utilize this strategy to modify plasma membrane protein composition should open up new areas of study in membrane biochemistry.